The mediating role of epigenetic clocks underlying educational inequalities in mortality: a multi-cohort study

Educational inequalities in mortality have been observed for decades, however the underlying biological mechanisms are not well known. We assessed the mediating role of altered aging of immune cells functioning captured by DNA methylation changes in blood (known as epigenetic clocks) in educational associated all-cause mortality. Data were from eight prospective population-based cohort studies, representing 13,021 participants. We found educational inequalities in mortality were larger for men than for women, estimated by hazard differences and ratios. Epigenetic clocks explained approximately 50% of educational inequalities in mortality for men, while the proportion was small for women. Most of this mediation was explained by differential effects of unhealthy lifestyles and morbidities of the WHO risk factors for premature mortality. These results support DNA methylation-based epigenetic aging as a signature of educational inequalities in life expectancy emphasizing the need for policies to address the unequal social distribution of these WHO risk factors.

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DNA methylation and lipid metabolism: an EWAS of 226 metabolic measures

Clinical Epigenetics ◽

10.1186/s13148-020-00957-8 ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Monica del C. Gomez-Alonso ◽

Anja Kretschmer ◽

Rory Wilson ◽

Liliane Pfeiffer ◽

Ville Karhunen ◽

...

Keyword(s):

Dna Methylation ◽

Lipid Metabolism ◽

Population Based ◽

Total Serum ◽

Resonance Spectroscopy ◽

Metabolic Disturbances ◽

Cpg Sites ◽

Gene Transcripts

Abstract Background The discovery of robust and trans-ethnically replicated DNA methylation markers of metabolic phenotypes, has hinted at a potential role of epigenetic mechanisms in lipid metabolism. However, DNA methylation and the lipid compositions and lipid concentrations of lipoprotein sizes have been scarcely studied. Here, we present an epigenome-wide association study (EWAS) (N = 5414 total) of mostly lipid-related metabolic measures, including a fine profiling of lipoproteins. As lipoproteins are the main players in the different stages of lipid metabolism, examination of epigenetic markers of detailed lipoprotein features might improve the diagnosis, prognosis, and treatment of metabolic disturbances. Results We conducted an EWAS of leukocyte DNA methylation and 226 metabolic measurements determined by nuclear magnetic resonance spectroscopy in the population-based KORA F4 study (N = 1662) and replicated the results in the LOLIPOP, NFBC1966, and YFS cohorts (N = 3752). Follow-up analyses in the discovery cohort included investigations into gene transcripts, metabolic-measure ratios for pathway analysis, and disease endpoints. We identified 161 associations (p value < 4.7 × 10−10), covering 16 CpG sites at 11 loci and 57 metabolic measures. Identified metabolic measures were primarily medium and small lipoproteins, and fatty acids. For apolipoprotein B-containing lipoproteins, the associations mainly involved triglyceride composition and concentrations of cholesterol esters, triglycerides, free cholesterol, and phospholipids. All associations for HDL lipoproteins involved triglyceride measures only. Associated metabolic measure ratios, proxies of enzymatic activity, highlight amino acid, glucose, and lipid pathways as being potentially epigenetically implicated. Five CpG sites in four genes were associated with differential expression of transcripts in blood or adipose tissue. CpG sites in ABCG1 and PHGDH showed associations with metabolic measures, gene transcription, and metabolic measure ratios and were additionally linked to obesity or previous myocardial infarction, extending previously reported observations. Conclusion Our study provides evidence of a link between DNA methylation and the lipid compositions and lipid concentrations of different lipoprotein size subclasses, thus offering in-depth insights into well-known associations of DNA methylation with total serum lipids. The results support detailed profiling of lipid metabolism to improve the molecular understanding of dyslipidemia and related disease mechanisms.

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Gene regulation contributes to explain the impact of early life socioeconomic disadvantage on adult inflammatory levels in two cohort studies

Scientific Reports ◽

10.1038/s41598-021-82714-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Cristian Carmeli ◽

Zoltán Kutalik ◽

Pashupati P. Mishra ◽

Eleonora Porcu ◽

Cyrille Delpierre ◽

...

Keyword(s):

Dna Methylation ◽

Gene Regulation ◽

Cohort Studies ◽

Early Life ◽

Life Experiences ◽

Socioeconomic Disadvantage ◽

Mediating Role ◽

The Impact ◽

The Relationship

AbstractIndividuals experiencing socioeconomic disadvantage in childhood have a higher rate of inflammation-related diseases decades later. Little is known about the mechanisms linking early life experiences to the functioning of the immune system in adulthood. To address this, we explore the relationship across social-to-biological layers of early life social exposures on levels of adulthood inflammation and the mediating role of gene regulatory mechanisms, epigenetic and transcriptomic profiling from blood, in 2,329 individuals from two European cohort studies. Consistently across both studies, we find transcriptional activity explains a substantive proportion (78% and 26%) of the estimated effect of early life disadvantaged social exposures on levels of adulthood inflammation. Furthermore, we show that mechanisms other than cis DNA methylation may regulate those transcriptional fingerprints. These results further our understanding of social-to-biological transitions by pinpointing the role of gene regulation that cannot fully be explained by differential cis DNA methylation.

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Longitudinal Course and Risk Factors for Fatigue in Adolescents: The Mediating Role of Sleep Disturbances

Journal of Pediatric Psychology ◽

10.1093/jpepsy/jst051 ◽

2013 ◽

Vol 38 (10) ◽

pp. 1070-1080 ◽

Cited By ~ 14

Author(s):

See Wan Tham ◽

Amy Lewandowski Holley ◽

Chuan Zhou ◽

Gregory N. Clarke ◽

Tonya M. Palermo

Keyword(s):

Risk Factors ◽

Sleep Disturbances ◽

Longitudinal Course ◽

Mediating Role

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Distress after a Single Violent Crime: How Shame-Proneness and Event-Related Shame Work Together as Risk Factors for Post-Victimization Symptoms

Psychological Reports ◽

10.2466/02.09.15.16.pr0.109.4.3-23 ◽

2011 ◽

Vol 109 (1) ◽

pp. 3-23 ◽

Cited By ~ 15

Author(s):

Olof Semb ◽

Lotta M.J. Strömsten ◽

Elisabet Sundbom ◽

Per Fransson ◽

Mikael Henningsson

Keyword(s):

Risk Factors ◽

Violent Crime ◽

Structural Equation ◽

Equation Modeling ◽

Mediating Role ◽

Shame Proneness ◽

Shame And Guilt ◽

Potential Risk Factors ◽

Guilt Proneness

To increase understanding of post-victimization symptom development, the present study investigated the role of shame- and guilt-proneness and event-related shame and guilt as potential risk factors. 35 individuals ( M age = 31.7 yr.; 48.5% women), recently victimized by a single event of severe violent crime, were assessed regarding shame- and guilt-proneness, event-related shame and guilt, and post-victimization symptoms. The mediating role of event-related shame was investigated with structural equation modeling (SEM), using bootstrapping. The guilt measures were unrelated to each other and to post-victimization symptoms. The shame measures were highly intercorrelated and were both positively correlated to more severe post-victimization symptom levels. Event-related shame as mediator between shame-proneness and post-victimization symptoms was demonstrated by prevalent significant indirect effects. Both shame measures are potent risk factors for distress after victimization, whereby part of the effect of shame-proneness on post-victimization symptoms is explained by event-related shame.

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Hostility and Increased Risk of Mortality and Acute Myocardial Infarction: The Mediating Role of Behavioral Risk Factors

American Journal of Epidemiology ◽

10.1093/oxfordjournals.aje.a009245 ◽

1997 ◽

Vol 146 (2) ◽

pp. 142-152 ◽

Cited By ~ 175

Author(s):

S. A. Everson ◽

J. Kauhanen ◽

G. A. Kaplan ◽

D. E. Goldberg ◽

J. Julkunen ◽

...

Keyword(s):

Risk Factors ◽

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Behavioral Risk Factors ◽

Behavioral Risk ◽

Mediating Role ◽

Risk Of Mortality ◽

Increased Risk

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Do Death Certificates Underestimate the Burden of Rare Diseases? The Example of Systemic Lupus Erythematosus Mortality, Sweden, 2001-2013

Public Health Reports ◽

10.1177/0033354918777253 ◽

2018 ◽

Vol 133 (4) ◽

pp. 481-488 ◽

Cited By ~ 8

Author(s):

Titilola Falasinnu ◽

Marios Rossides ◽

Yashaar Chaichian ◽

Julia F. Simard

Keyword(s):

Systemic Lupus Erythematosus ◽

Cause Of Death ◽

Rare Diseases ◽

Lupus Erythematosus ◽

Health Resources ◽

Premature Mortality ◽

Population Based ◽

Mortality Data ◽

Systemic Lupus ◽

Swedish Population

Objectives: Mortality due to rare diseases, which are substantial sources of premature mortality, is underreported in mortality studies. The objective of this study was to determine the completeness of reporting systemic lupus erythematosus (SLE) as a cause of death. Methods: In 2017, we linked data on a Swedish population-based cohort (the Swedish Lupus Linkage, 2001-2013) comprising people with SLE (n = 8560) and their matched general population comparators (n = 37 717) to data from the Cause of Death Register. We reviewed death records of deceased people from the cohort (n = 5110) and extracted data on patient demographic characteristics and causes of death. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) for not reporting SLE as a cause of death by using multivariable-adjusted logistic regression models. Results: Of 1802 deaths among SLE patients in the study, 1071 (59%) did not have SLE reported on their death records. Most SLE decedents were aged 75-84 at death (n = 584, 32%), female (n = 1462, 81%), and born in Nordic countries (n = 1730, 96%). Decedents aged ≥85 at death were more likely to have SLE not reported on their death records than were decedents aged <50 (OR = 2.34; 95% CI, 1.48-3.68). Having renal failure listed as a cause of death decreased the likelihood of SLE not being reported on the death record (OR = 0.54; 95% CI, 0.40-0.73), whereas having cancer listed as a cause of death increased this likelihood (OR = 2.39; 95% CI, 1.85-3.07). Conclusions: SLE was greatly underreported as a cause of mortality on death records of SLE patients, particularly in older decedents and those with cancer, thereby underestimating the true burden of this disease. Public health resources need to focus on improving the recording of rare diseases in order to enhance the epidemiological utility of mortality data.

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Association of birthplace and occupational exposures with chronic bronchitis in US Hispanics/Latinos, 2008–2011

Occupational and Environmental Medicine ◽

10.1136/oemed-2019-106081 ◽

2020 ◽

Vol 77 (5) ◽

pp. 344-350 ◽

Cited By ~ 1

Author(s):

Victor Kim ◽

Wei Wang ◽

David Mannino ◽

Alejandro Diaz

Keyword(s):

Risk Factors ◽

Chronic Bronchitis ◽

Occupational Exposures ◽

Population Based ◽

Central American ◽

Health Study ◽

Mortality Data ◽

South American ◽

Hispanic Community ◽

American Heritage

ObjectivesIn the US, chronic bronchitis (CB) is common and is associated with substantial morbidity and mortality. Data on CB in the Hispanic/Latino population—a large, diverse US minority—are scarce. We aimed to test whether the prevalence of CB varies across Hispanic/Latino heritages and to identify CB risk factors, including occupational exposures, in this population.MethodsWe analysed data from the Hispanic Community Health Study/Study of Latinos, a US population-based probability sample of participants aged 18–74 years (n=16 415) including those with Mexican, Puerto Rican, Dominican, Cuban, Central American and South American heritages. Participants who had a completed respiratory questionnaire and valid spirometric data were included in the analysis (n=13 259). CB, place of birth, heritage, occupational exposures and other risk factors were based on standardised questionnaires. The prevalence of CB was estimated using survey logistic regression-conditional marginal analysis.ResultsThe estimated (mean (95% CI)) overall adjusted prevalence of CB was 12.1% (9.3 to 15.6), with a large variation across heritages. Dominican heritage had a fivefold higher prevalence than South American heritage. US-born participants had a higher adjusted prevalence than their non-US-born counterparts (16.8% (12.5 to 22.1) vs 11.0% (8.5 to 14.10); p=0.022). Compared with non-exposed participants, those exposed to cleaning or disinfecting solutions had a higher adjusted prevalence of CB (12.6% (9.1 to 17.1) vs 11.8% (9.2 to 15.1); p=0.024).ConclusionsThe prevalence of CB was higher among Dominicans than other Hispanic/Latino heritages. CB was more prevalent among US-born participants and those exposed to cleaning and disinfecting solutions.

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